ClinVar Miner

Submissions for variant NM_014141.6(CNTNAP2):c.1123C>T (p.Pro375Ser)

gnomAD frequency: 0.00002  dbSNP: rs757993314
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519886 SCV000621924 uncertain significance not provided 2020-01-02 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001039684 SCV001203225 uncertain significance Cortical dysplasia-focal epilepsy syndrome 2022-10-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 375 of the CNTNAP2 protein (p.Pro375Ser). This variant is present in population databases (rs757993314, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 453068). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002438263 SCV002750661 uncertain significance Inborn genetic diseases 2018-07-27 criteria provided, single submitter clinical testing The p.P375S variant (also known as c.1123C>T), located in coding exon 8 of the CNTNAP2 gene, results from a C to T substitution at nucleotide position 1123. The proline at codon 375 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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